Puberty, pregnancy, and menopause show shared and distinct structural changes across the lifespan.

Abstract

The female brain undergoes substantial reorganization during major hormonal transitions, yet whether puberty, pregnancy, and menopause engage shared or distinct neuroplastic mechanisms remains unknown. We compared longitudinal structural brain changes across all three major hormonal life events using identical analytical methods within a single cohort framework (n = 1095), with stable control groups to control for normative developmental and aging trajectories. Both pre-to-post menarche and pre-to-post pregnancy groups showed widespread cortical gray matter reductions, with cross-cohort comparisons revealing divergent profiles across more than half of cortical regions alongside convergence in prefrontal, parietal, and temporal association cortices. Pre-to-post menopausal women showed a fundamental divergence from both puberty and pregnancy, as they showed no volumetric loss, while stable pre- and postmenopausal control groups did. Puberty and pregnancy thus share both convergent and divergent cortical remodeling, while menopause represents a qualitatively distinct pattern, defined by the absence rather than acceleration of volumetric change.